Specific radioimmunotherapy using 90Y-labeled monoclonal antibody in erythroleukemic mice

Abstract

Radioimmunotherapy using 90Y-labeled diethylenetriamine pentaacetic acid-antibody conjugates was studied in Rauscher erythroleukemia virus-infected mice. Preliminary experiments showed that biodistribution profiles for nonrelevant mouse monoclonal antibody and polyclonal bovine immunoglobulin were identical in both normal and leukemic mice. Therefore, bovine immunoglobulin G was selected as the control immunoglobulin in order to permit comparison to current clinical trials of radioimmunotherapy regimens. Specific monoclonal antibody was two- to three-fold more potent than bovine immunoglobulin G in therapy, as assessed by reduction of splenomegaly (dose required for half-maximal effect, 9 microCi versus 16 to 27 microCi). Mice treated with 50 microCi 90Y-labeled control immunoglobulin had spleens which were twice the normal size and showed extensive areas of erythropoiesis indicative of the presence of tumor foci; in contrast, doses as low as 27 microCi 90Y-labeled specific antibody resulted in complete remission with no microscopic evidence of tumor foci in either spleen or liver. Although reversible marrow toxicity was observed it was not dose limiting. These results demonstrate that tumor-specific therapy is possible using 90Y-labeled antibody.